留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码
x 关闭 永久关闭

应中央军委要求，2022年9月起，《药学实践杂志》将更名为《药学实践与服务》，双月刊，正文96页；2023年1月起，拟出版月刊，正文64页，数据库收录情况与原《药学实践杂志》相同。欢迎作者踊跃投稿！

建立以HIF-1α为靶标的高通量筛选防治动脉粥样硬化先导化合物的细胞模型

钱俞君,  秦春霞,  孙莉莉,  丁华敏,  李铁军

downloadPDF
文章导航 > 药学实践与服务  > 2019 >  37(1): 27-31
钱俞君, 秦春霞, 孙莉莉, 丁华敏, 李铁军. 建立以HIF-1α为靶标的高通量筛选防治动脉粥样硬化先导化合物的细胞模型[J]. 药学实践与服务, 2019, 37(1): 27-31. doi: 10.3969/j.issn.1006-0111.2019.01.007
引用本文: 钱俞君, 秦春霞, 孙莉莉, 丁华敏, 李铁军. 建立以HIF-1α为靶标的高通量筛选防治动脉粥样硬化先导化合物的细胞模型[J]. 药学实践与服务, 2019, 37(1): 27-31. doi: 10.3969/j.issn.1006-0111.2019.01.007
shu
QIAN Yujun, QIN Chunxia, SUN Lili, DING Huamin, LI Tiejun. A cell model for high-throughput screening lead compounds targeting HIF-1α for atherosclerosis treatment[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(1): 27-31. doi: 10.3969/j.issn.1006-0111.2019.01.007
Citation: QIAN Yujun, QIN Chunxia, SUN Lili, DING Huamin, LI Tiejun. A cell model for high-throughput screening lead compounds targeting HIF-1α for atherosclerosis treatment[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(1): 27-31. doi: 10.3969/j.issn.1006-0111.2019.01.007
shu

建立以HIF-1α为靶标的高通量筛选防治动脉粥样硬化先导化合物的细胞模型

doi: 10.3969/j.issn.1006-0111.2019.01.007

  • 上海市浦东新区浦南医院药剂科, 上海 200125

基金项目: 上海市浦东新区科技发展基金（PKJ2015-Y26）；上海市浦东新区卫生和计划生育委员会学科建设（PWZbr2017-16）

A cell model for high-throughput screening lead compounds targeting HIF-1α for atherosclerosis treatment

  • Department of Pharmacy, Punan Hospital of Pudong New Area, Shanghai 200125, China

  • 摘要: 目的 建立一个高通量筛选防治动脉粥样硬化先导化合物的体外细胞模型。 方法 克隆HIF-1α低氧反应元件（hypoxia response element，HRE）至荧光素酶报告基因表达载体pGL3-Enhancer，构建荧光素酶表达载体pGL3-HIF-1α-HRE，转染人单核细胞THP-1并筛选稳定表达细胞株THP-1-HIF-1α-HRE。 结果 Real Time-PCR检测表明低氧培养可以有效上调THP-1-HIF-1α-HRE细胞HIF-1α蛋白表达和荧光素酶活性，而洛伐他汀和姜黄素预处理可以有效抑制低氧引起的THP-1-HIF-1α-HRE细胞内HIF-1α蛋白表达及荧光素酶活性。 结论 成功建立了筛选抗动脉粥样硬化的先导化合物体外高通量细胞模型THP1-HIF-1α-HRE。
    Abstract: Objective To establish a high-throughput in-vitro screening cell model for anti-atherosclerosis leading compounds. Methods Hypoxia response element (HRE) was cloned into a luciferase reporter vector, pGL3-Enhancer, to construct pGL3-HIF-1α-HRE. The THP-1 human monocyte cell line was infected with the pGL3-HIF-1α-HRE and a stable cell line, THP-1-HIF-1α-HRE, was screened. Results Real-time PCR assay showed that HIF-1α expression and luciferase activity in THP-1-HIF-1α-HRE cells was effectively upregulated by hypoxia. The increase of HIF-1α expression and luciferase activity induced by hypoxia was significantly inhibited by lovastatin or curcumin. Conclusion THP1-HIF-1α-HRE, an in-vitro cell model for high-throughput screening lead compounds for anti-atherosclerosis (AS) was successfully established.
  • [1] ROSS R. Atherosclerosis-an inflammatory disease[J].New Engl J Med, 1999, 340(2):115-126.
    [2] KALIORA A C, DEDOUSSIS G V Z, SCHMIDT H. Dietary antioxidants in preventing atherogenesis[J]. Atherosclerosis, 2006, 187(1):1-17.
    [3] LIM C S, KIRIAKIDIS S, SANDISON A, et al. Hypoxia-inducible factor pathway and diseases of the vascular wall[J]. J Vasc Surg, 2013, 58(1):219-230.
    [4] PARATHATH S, MICK S L, FEIG J E,et al. Hypoxia is present in murine atherosclerotic plaques and has multiple adverse effects on macrophage lipid metabolism[J]. Circ Res, 2011, 109(10):1141-1152.
    [5] PARATHATH S, YANG Y, MICK S, et al. Hypoxia in murine atherosclerotic plaques and its adverse effects on macrophages[J]. Trends Cardiovasc Med, 2013, 23(3):80-84.
    [6] SCHOLZ C C, TAYLOR C T. Targeting the HIF pathway in inflammation and immunity[J]. Curr Opin Pharmacol, 2013, 13(4):646-653.
    [7] MAZI RE C, MAZI RE J C. Activation of transcription factors and gene expression by oxidized low-density lipoprotein[J]. Free Radic Bio Med, 2009, 46(2):127-137.
    [8] RODR GUEZ J A, NESPEREIRA B, P REZ-ILZARBE M, et al. Vitamins C and E prevent endothelial VEGF and VEGFR-2 overexpression induced by porcine hypercholesterolemic LDL[J].Cardiovasc Res, 2005,65(3):665-673.
    [9] ZHU X Y, RODRIGUEZ-PORCEL M, BENTLEY M D, et al. Antioxidant intervention attenuates myocardial neovascularization in hypercholesterolemia[J]. Circulation, 2004, 109(17):2109-2115.
    [10] SHATROV V A. Oxidized low-density lipoprotein (ox-LDL) triggers hypoxia-inducible factor-1α (HIF-1α) accumulation via redox-dependent mechanisms[J]. Blood, 2003,101(12):4847-4849.
    [11] JIANG G, LI T, QIU Y, et al. RNA interference for HIF-1α inhibits foam cells formation in vitro[J]. Eur J Pharmacol, 2007, 562(3):183-190.
    [12] MANOLESCU B, OPREA E, BUSU C, et al. Natural compounds and the hypoxia-inducible factor (HIF) signalling pathway[J]. Biochimie, 2009, 91(11-12):1347-1358.
    [13] WILSON S H,HERRMANN J, LERMAN L O, et al. Simvastatin preserves the structure of coronary adventitial vasa vasorum in experimental hypercholesterolemia independent of lipid lowering[J]. Circulation, 2002,105(4):415-418.
    [14] DICHTL W. HMG-CoA reductase inhibitors regulate inflammatory transcription factors in human endothelial and vascular smooth muscle cells[J]. Arterioscler Thromb Vasc Biol, 2002, 23(1):58-63.
    [15] HOSSAIN C F, KIM Y P, BAERSON S R, et al. Saururus cernuus lignans-potent small molecule inhibitors of hypoxia-inducible factor-1[J]. Biochem Biophys Res Commun, 2005, 333(3):1026-1033.
  • [1] 冯志惠, 邓仪卿, 叶冰, 安培, 张宏, 张海军.  雀梅藤石油醚提取物诱导三阴性乳腺癌细胞凋亡的实验研究 . 药学实践与服务, 2024, 42(6): 253-259. doi: 10.12206/j.issn.2097-2024.202311055
    [2] 赖立勇, 夏天爽, 徐圣焱, 蒋益萍, 岳小强, 辛海量.  中药青蒿抗氧化活性的谱效关系研究 . 药学实践与服务, 2024, 42(5): 203-210, 216. doi: 10.12206/j.issn.2097-2024.202211012
  • 加载中
WeChat 点击查看大图
计量
  • 文章访问数:  2670
  • HTML全文浏览量:  342
  • PDF下载量:  382
  • 被引次数: 0
出版历程
  • 收稿日期:  2018-06-11
  • 修回日期:  2018-09-25

建立以HIF-1α为靶标的高通量筛选防治动脉粥样硬化先导化合物的细胞模型

doi: 10.3969/j.issn.1006-0111.2019.01.007
  • 上海市浦东新区浦南医院药剂科, 上海 200125
    • 基金项目:  上海市浦东新区科技发展基金（PKJ2015-Y26）；上海市浦东新区卫生和计划生育委员会学科建设（PWZbr2017-16）
  • 收稿日期: 2018-06-11
  • 修回日期: 2018-09-25

摘要: 目的 建立一个高通量筛选防治动脉粥样硬化先导化合物的体外细胞模型。 方法 克隆HIF-1α低氧反应元件（hypoxia response element，HRE）至荧光素酶报告基因表达载体pGL3-Enhancer，构建荧光素酶表达载体pGL3-HIF-1α-HRE，转染人单核细胞THP-1并筛选稳定表达细胞株THP-1-HIF-1α-HRE。 结果 Real Time-PCR检测表明低氧培养可以有效上调THP-1-HIF-1α-HRE细胞HIF-1α蛋白表达和荧光素酶活性，而洛伐他汀和姜黄素预处理可以有效抑制低氧引起的THP-1-HIF-1α-HRE细胞内HIF-1α蛋白表达及荧光素酶活性。 结论 成功建立了筛选抗动脉粥样硬化的先导化合物体外高通量细胞模型THP1-HIF-1α-HRE。

English Abstract

钱俞君, 秦春霞, 孙莉莉, 丁华敏, 李铁军. 建立以HIF-1α为靶标的高通量筛选防治动脉粥样硬化先导化合物的细胞模型[J]. 药学实践与服务, 2019, 37(1): 27-31. doi: 10.3969/j.issn.1006-0111.2019.01.007
引用本文: 钱俞君, 秦春霞, 孙莉莉, 丁华敏, 李铁军. 建立以HIF-1α为靶标的高通量筛选防治动脉粥样硬化先导化合物的细胞模型[J]. 药学实践与服务, 2019, 37(1): 27-31. doi: 10.3969/j.issn.1006-0111.2019.01.007
shu
QIAN Yujun, QIN Chunxia, SUN Lili, DING Huamin, LI Tiejun. A cell model for high-throughput screening lead compounds targeting HIF-1α for atherosclerosis treatment[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(1): 27-31. doi: 10.3969/j.issn.1006-0111.2019.01.007
Citation: QIAN Yujun, QIN Chunxia, SUN Lili, DING Huamin, LI Tiejun. A cell model for high-throughput screening lead compounds targeting HIF-1α for atherosclerosis treatment[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(1): 27-31. doi: 10.3969/j.issn.1006-0111.2019.01.007
shu

    全文HTML

参考文献 (15)

目录

    /

    返回文章
    返回

    版权所有：《药学实践与服务》编辑委员会

    主管、主办: 中国人民解放军海军军医大学地址: 上海市杨浦区国和路325号邮政编码: 200433

    电话: （021）81871324,81871397 E-mail: yxsjzzs@163.com

    网站备案号 沪ICP备05003363号-1

    本系统由 北京仁和汇智信息技术有限公司 开发    百度统计